Interpretive Summary: Marek’s disease (MD) is a virus induced disease of chicken that continues to threaten the prosperity of the poultry industry worldwide. To better control the disease, genetic and epigenetic (heritable control other than that of DNA) mechanisms underlying of host resistance to MD have been actively sought by the industry and research communities to augment current control measures including vaccination and management of the flocks. This study reports findings of DNA methylation, a chemical modification of DNA chain of specific structural property, differences between a MD resistant line and a susceptible line of chickens post MDV infection. In addition to common DNA methylation patterns, many different patterns were identified between the two lines. The findings suggest DNA methylation may be associated with chicken disease resistance and susceptibility.

Technical Abstract:
Marek’s disease (MD) is characterized as a T cell lymphoma induced by a cell-associated a-herpesvirus, Marek’s disease virus type 1 (MDV1). As with many viral infectious diseases, DNA methylation variations were observed in the progression of MD; these variations are thought to play an important role in host-virus interactions. We observed that DNA methyltransferase 3a (DNMT3a) and 3b (DNMT3b) were differentially expressed in chicken MD-resistant line 63 and MDsusceptible line 72 at 21 d after MDV infection. To better understand the role of methylation variation induced by MDV infection in both chicken lines, we mapped the genome-wide DNA methylation profiles in each line using Methyl-MAPS (methylation mapping analysis by paired-end sequencing). Collectively, the data sets collected in this study provide a more comprehensive picture of the chicken methylome. Overall, methylation levels were reduced in chickens from the resistant line 63 after MDV infection. We identified 11,512 infection-induced differential methylation regions (iDMRs). The number of iDMRs was larger in line 72 than in line 63, and most of iDMRs found in line 63 were overlapped with the iDMRs found in line 72. We further showed that in vitro methylation levels were associated with MDV replication, and found that MDV propagation in the infected cells was restricted by pharmacological inhibition of DNA methylation. Our results suggest that DNA methylation in the host may be associated with disease resistance or susceptibility. The methylation variations induced by viral infection may consequentially change the host transcriptome and result in diverse disease
outcomes.